The dynamic changes that characterize the female reproductive system are regulated by hormones. However, local cell-to-cell interactions may mediate responsiveness of tissues to hormonal signals. The corpus luteum (CL) is an excellent model for understanding how immune cells are recruited into tissues and the role played by those cells in regulating tissue homeostasis or demise. Leukocytes are recruited into the CL throughout its lifespan, and leukocyte-derived cytokines have been found in corpora lutea of all species examined. The proinflammatory cytokines inhibit gonadotropin-stimulated steroidogenesis, profoundly stimulate prostaglandin synthesis by luteal cells, and promote apoptosis. However, there is mounting evidence that leukocytes and luteal cells communicate in different ways to maintain homeostasis within the functional CL. Domestic animals have provided important information regarding the presence and role of immune cells in the CL.